Prochlorperazine (Compazine) | Medication Reference

Bedside Snapshot

Core Use: Phenothiazine antipsychotic used at lower doses primarily as a potent antiemetic and migraine adjunct; at higher doses has antipsychotic effects
Onset/Duration: IV/IM onset 5–20 minutes; oral/rectal onset 30–60 minutes; duration ~6–12 hours
Key Danger: Acute dystonic reactions, akathisia, sedation, orthostatic hypotension, QT prolongation, and rare neuroleptic malignant syndrome (NMS)
Special Note: Often paired with diphenhydramine 25–50 mg IV/IM to reduce risk of extrapyramidal symptoms; use caution in elderly and those with cardiac disease

Contraindications

Absolute Contraindications:

Known hypersensitivity to prochlorperazine or other phenothiazines
Comatose states or severe CNS depression from any cause (e.g., concurrent high-dose CNS depressants)
Children under 2 years of age or <9 kg
Severe hypotension or circulatory collapse (relative/strong caution)

Major Precautions:

Elderly patients with dementia-related psychosis have an increased risk of death with antipsychotic drugs (class boxed warning); minimize dose and duration
Use cautiously in patients with QT prolongation, electrolyte abnormalities, or those on other QT-prolonging drugs (e.g., certain antiarrhythmics, macrolides, fluoroquinolones)
May lower seizure threshold; caution in patients with seizure disorders or on other pro-convulsant medications
Orthostatic hypotension and sedation are common; monitor hemodynamics in volume-depleted or critically ill patients
History of extrapyramidal symptoms (EPS) or parkinsonism: prochlorperazine can worsen motor symptoms; consider alternatives
Pregnancy: generally avoided in the first trimester unless benefits clearly outweigh risks; short-term use for refractory hyperemesis may be considered under obstetric guidance

⚠️ Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. Prochlorperazine is not approved for dementia-related psychosis.

Adverse Effects

Common:

Sedation, dizziness, fatigue
Orthostatic hypotension, mild tachycardia
Dry mouth, constipation, blurred vision (anticholinergic effects)
Injection-site pain (IM) or irritation (IV)

Serious:

Extrapyramidal symptoms (EPS): acute dystonia (torticollis, oculogyric crisis), akathisia, parkinsonism
Neuroleptic malignant syndrome (NMS): hyperthermia, rigidity, autonomic instability, altered mental status
Tardive dyskinesia with chronic use, especially in elderly women
QT prolongation and torsades de pointes, particularly with other risk factors (hypokalemia, hypomagnesemia, other QT-prolonging medications)
Severe hypotension, syncope, or arrhythmias, especially with IV dosing
Hematologic effects (rare): leukopenia, agranulocytosis; monitor for signs of infection with prolonged therapy

Monitoring

Clinical Monitoring:

Clinical response: resolution of nausea/vomiting or migraine symptoms; reassess for alternative diagnosis if no benefit
Mental status, level of sedation, and ability to protect airway, especially in combination with opioids or other sedatives
Blood pressure and heart rate (watch for orthostatic hypotension and tachycardia)
Neurologic exam for early signs of EPS (restlessness, neck stiffness, oculogyric crisis, tongue protrusion)

Laboratory/Diagnostic Monitoring:

ECG monitoring in high-risk patients (known QT prolongation, on other QT-prolonging drugs, or significant electrolyte disturbances)
Electrolytes (potassium, magnesium) in patients at risk for QT prolongation

Drug Names & Classification

Generic Name: Prochlorperazine

Brand Names: Compazine, Compro (generic available)

Drug Class: Phenothiazine derivative; dopamine (D₂) receptor antagonist; antipsychotic and antiemetic

Mechanism of Action

Blocks dopamine D₂ receptors in the chemoreceptor trigger zone (CTZ) of the medulla, reducing stimulation of the vomiting center and thereby decreasing nausea and vomiting
At higher or repeated doses, antagonism of D₂ receptors in mesolimbic pathways contributes to antipsychotic effects
Exhibits alpha-adrenergic, anticholinergic (muscarinic), and antihistaminic activity, contributing to sedation, orthostatic hypotension, and some of its side-effect profile
Like other phenothiazines, can affect cardiac repolarization (QT prolongation) and lower seizure threshold

Pharmacokinetics

Absorption: Oral and rectal formulations are well absorbed; onset of antiemetic effect within 30–60 minutes by mouth or rectal; IV/IM onset typically within 5–20 minutes
Distribution: Highly protein bound; widely distributed, including CNS; relatively large volume of distribution consistent with lipophilicity
Metabolism: Primarily hepatic via oxidative pathways; subject to first-pass metabolism with oral administration
Elimination: Metabolites excreted in urine and feces; terminal half-life roughly 6–12 hours, allowing q6h dosing for antiemetic use
Special Populations: Hepatic impairment can increase exposure; use lower doses and monitor for adverse CNS effects in liver disease and the elderly

Common ED/ICU Indications

Symptomatic treatment of nausea and vomiting due to a variety of causes (e.g., migraine, gastroenteritis, medication-related) once emergent etiologies are addressed
Adjunct treatment of acute migraine in the ED, often combined with diphenhydramine and IV fluids with or without NSAIDs
Short-term control of severe nausea and vomiting associated with chemotherapy (historically; now often secondary to newer antiemetics)
Antipsychotic use (e.g., schizophrenia) is less common in ED/ICU where other agents (e.g., haloperidol) are usually preferred

Available Forms & Strengths

Injection (IV/IM): Commonly 5 mg/mL in 2 mL vials (10 mg total per vial; may vary by product)
Tablets: 5 mg, 10 mg immediate-release tablets
Rectal Suppositories: 25 mg (often dosed every 12 hours)
Oral Liquid: Formulations exist in some markets; verify concentration prior to dosing

Dosing – Prochlorperazine (Adult Antiemetic/Migraine)

Always follow local guidelines and institutional protocols.

Route / Scenario	Typical Dose	Frequency	Notes
IV Antiemetic / Migraine	10 mg IV	Once; may repeat every 4–6 hours as needed	Give slowly over 2–5 minutes; often pair with 25–50 mg diphenhydramine IV
IM Antiemetic / Migraine	10 mg IM	Once; may repeat every 3–4 hours as needed	Onset slower than IV; monitor for sedation, hypotension
PO Antiemetic (short-term)	5–10 mg PO	Every 6–8 hours as needed	Max typical total about 40 mg/day; use lowest effective dose
Rectal Suppository	25 mg PR	Every 12 hours as needed	Useful when vomiting prevents PO use and IV access is not available
Elderly or Frail	2.5–5 mg IV/IM/PO	Every 6–8 hours as needed	Higher risk of EPS, sedation, orthostatic hypotension; titrate cautiously
Maximum Daily Dose	30–40 mg/day	Divided doses	Higher doses approach antipsychotic ranges and increase side effects
Antipsychotic Dosing	5–10 mg PO/IM	Every 6–8 hours; titrate per psychiatry	ED/ICU use is uncommon; usually other agents preferred

Pediatric Use (outline):

Avoid use in children under 2 years of age or <9 kg due to increased risk of extrapyramidal reactions and respiratory depression
In older children, use is restricted and alternative antiemetics (e.g., ondansetron) are often preferred for routine nausea and vomiting
If used, dosing is weight-based with tight age/weight restrictions and maximums; follow institutional pediatric guidelines strictly

Clinical Pearls

💡 Co-administration with Diphenhydramine: In the ED, prochlorperazine 10 mg IV/IM is often paired with diphenhydramine 25–50 mg IV/IM to reduce the risk of acute dystonic reactions and akathisia.

⚠️ Acute Dystonia Treatment: If acute dystonia occurs (e.g., neck spasm, oculogyric crisis), treat promptly with diphenhydramine or benztropine and avoid further phenothiazine use.

ℹ️ Ondansetron vs. Prochlorperazine: Ondansetron is often preferred for routine nausea due to a more favorable side-effect profile, but prochlorperazine can be very helpful in migraine-associated nausea or when ondansetron fails.

⚠️ Special Caution in Older Adults: Elderly patients are much more prone to EPS, orthostatic hypotension, and sedation; start low and go slow. Consider alternative antiemetics when possible.

💡 QT Prolongation Risk: Check for other QT-prolonging medications and correct electrolytes (potassium, magnesium) before and during therapy in high-risk cardiac patients.

ℹ️ IV Administration: Always administer IV prochlorperazine slowly over 2–5 minutes to minimize risk of hypotension and other adverse effects.

References

Lexicomp. (2024). Prochlorperazine: Drug information. Wolters Kluwer.
Tintinalli, J. E., Ma, O. J., & Yealy, D. M. (2016). Tintinalli's emergency medicine: A comprehensive study guide (8th ed.). McGraw-Hill Education.
American Headache Society. (2016). Management of adults with acute migraine in the emergency department. Headache, 56(6), 911–940. https://doi.org/10.1111/head.12864
U.S. Food and Drug Administration. (2024). Compazine (prochlorperazine) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/011717s043lbl.pdf
Friedman, B. W., Esses, D., Solorzano, C., Choi, H. K., Cole, M., Davitt, M., Bijur, P. E., & Gallagher, E. J. (2008). A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Annals of Emergency Medicine, 52(4), 399–406. https://doi.org/10.1016/j.annemergmed.2008.01.333